Health of mom's gut a key contributor to autism risk

Could reducing risk of autism involve changing expectant mothers' diets?

July 18, 2018

Science Daily/University of Virginia Health System

The mother's microbiome, the collection of microscopic organisms that live inside us, is a key contributor to the risk of autism and other neurodevelopmental disorders in her offspring, new research suggests. The work raises the possibility that we could help prevent autism by altering expectant moms' diets.

Further, the UVA scientists were able to use their discovery to prevent the development of autism-like neurodevelopmental disorders in lab mice. They found they could halt the development of such disorders by blocking a particular inflammatory molecule produced by the immune system. Targeting this molecule, interleukin-17a, offers another potential avenue for preventing autism in people, the researchers say. They caution, however, that this approach would be much more complex because of the risk of side effects.

"We determined that the microbiome is a key contributor in determining susceptibility [to autism-like disorders], so it suggests that you could target either the maternal microbiome or this inflammatory molecule, IL-17a," said lead researcher John Lukens, PhD, of UVA's Department of Neuroscience. "You could also use this [IL-17a] as a biomarker for early diagnosis."

The groundbreaking work from Lukens and his colleagues sheds light on the complex relationship between the health of the mother's microbiome and the healthy development of her children. "The microbiome can shape the developing brain in multiple ways," explained Lukens, of UVA's Center for Brain Immunology and Glia (BIG) and UVA's Carter Immunology Center. "The microbiome is really important to the calibration of how the offspring's immune system is going to respond to an infection or injury or stress."

But an unhealthy microbiome in the mom can create problems: Lukens' work shows that it can make her unborn offspring susceptible to neurodevelopmental disorders. The researchers found that the IL-17a molecule was a key contributor to the development of autism-like symptoms in lab mice.

The good news: The microbiome can be modified easily, either through diet, probiotic supplements or fecal transplant. All of these approaches seek to restore a healthy equilibrium among the different microorganisms that live in the gut.

"In terms of translating our work to humans, I think the next big step would be to identify features of the microbiome in pregnant mothers that correlate with autism risk," Lukens said. "I think the really important thing is to figure out what kind of things can be used to modulate the microbiome in the mother as effectively and safely as we can."

Another Option for Preventing Autism

Blocking IL-17a also might offer a way to prevent autism, but Lukens said that path carries much more risk. "If you think about pregnancy, the body is basically accepting foreign tissue, which is a baby," he said. "As a result, maintenance of embryonic health demands a complex balance of immune regulation, so people tend to shy away from manipulating the immune system during pregnancy."

IL-17a previously has been implicated in conditions such as rheumatoid arthritis, multiple sclerosis and psoriasis, and there are already drugs available that target it. But Lukens noted that the molecule has an important purpose in stopping infections, especially fungal infections. Blocking it, he said, "could make you susceptible to all kinds of infections." And doing so during pregnancy could have complex ripple effects on a child's development that scientists would need to sort out.

For their next steps, Lukens and his team plan to explore the potential role of other immune molecules in the development of autism and other such conditions. IL-17a may be just one piece in a much larger puzzle, he said.

While Lukens' work links the immune system with neurodevelopmental disorders, he emphasized that this in no way suggests that vaccines are contributing to the development of autism. "There's a definite link between the immune response and the developing brain," he said. "It just doesn't have anything to do with vaccines. It's much, much earlier."

Lukens' work is but the latest research from UVA to speak to the importance of the microbiome in maintaining good health. For example, one of Lukens' colleagues in the Department of Neuroscience, Alban Gaultier, PhD, found that probiotics in yogurt can reverse depression symptoms.

https://www.sciencedaily.com/releases/2018/07/180718113343.htm

Stress exposure during pregnancy observed in mothers of children with autism

More research needed to understand gene-stress interaction

June 7, 2016

Science Daily/University of Missouri-Columbia

Stress during pregnancy has been linked to several conditions, including some instances of autism spectrum disorder. Now, researchers have observed a variant of a stress-sensitive gene and exposure to stress during pregnancy among two groups of mothers of children with autism. The finding could be a step toward helping identify women who have greater risks for having children with autism when exposed to stressors during pregnancy.

"Autism was thought to be largely a genetic disorder, but previous research has shown that environmental influences such as stress can play an important role in the development of the condition," said David Beversdorf, M.D., associate professor in the departments of radiology, neurology and psychological sciences at the University of Missouri and the MU Thompson Center for Autism and Neurodevelopmental Disorders, and senior author of the study. "We know that some mothers who experience significant levels of stress don't have children with autism, but others do. To help understand why, we studied a gene that is known to affect stress and found a link between it and the development of autism with exposure to stress."

Led by Beversdorf's graduate student, Patrick Hecht, Ph.D., in collaboration with Xudong Liu, Ph.D., with Queen's University in Ontario, Canada, the researchers studied two separate groups of mothers of children with autism spectrum disorder -- a group of families at MU and a group of families at Queen's University. The mothers were surveyed about stress during their pregnancy, such as loss of a job, moving or divorce. The mothers' blood was tested for a variation of the stress-sensitive gene known as 5-HTTLPR, which regulates the neurotransmitter serotonin in the nervous system. When a variation of the gene is present, the availability of serotonin is altered, causing an increased reaction to stress.

In both groups, mothers of children with autism who have the variation of the stress-sensitive gene reported experiencing more stress during the end of the second and the beginning of the third trimester of pregnancy, compared to mothers who did not carry the altered gene.

"Though this was an observational study and future confirmation of this finding is needed, it's possible we could, one day, identify women who may be at a greater risk of having a child with autism when exposed to stress," said Beversdorf, who also serves as the William and Nancy Thompson Endowed Chair in Radiology. "More research is needed to understand the mechanisms of how this gene-stress interaction works, but hopefully this could someday help prevent some cases of autism."

https://www.sciencedaily.com/releases/2016/06/160607220116.htm

Fine particulate air pollution linked with increased autism risk

December 18, 2014

Science Daily/Harvard School of Public Health

Women exposed to high levels of fine particulate matter specifically during pregnancy -- particularly during the third trimester -- may face up to twice the risk of having a child with autism than mothers living in areas with low particulate matter, according to a study. The greater the exposure, the greater the risk, researchers found. It was the first US-wide study exploring the link between airborne particulate matter and autism.

"Our data add additional important support to the hypothesis that maternal exposure to air pollution contributes to the risk of autism spectrum disorders," said Marc Weisskopf, associate professor of environmental and occupational epidemiology and senior author of the study. "The specificity of our findings for the pregnancy period, and third trimester in particular, rules out many other possible explanations for these findings."

The researchers explored the association between autism and exposure to PM2.5 before, during, and after pregnancy. They also calculated exposure to PM2.5 during each pregnancy trimester.

Exposure to PM2.5 was significantly associated with autism during pregnancy, but not before or after, the study found. And during the pregnancy, the third trimester specifically was significantly associated with an increased risk. Little association was found between air pollution from larger-sized particles (PM10-2.5) and autism.

"The evidence base for a role for maternal exposure to air pollution increasing the risk of autism spectrum disorders is becoming quite strong," said Weisskopf. "This not only gives us important insight as we continue to pursue the origins of autism spectrum disorders, but as a modifiable exposure, opens the door to thinking about possible preventative measures."

http://www.sciencedaily.com/releases/2014/12/141218081334.htm